Scutellaria baicalensis Georgi, a commonly used herb in Chinese medicine, could
facilitate oral absorption of drugs and overcome multidrug resistance in cancer caused
by P-glycoprotein 170
 

Yashang Lee 1, Shwu-Huey Liu 2, Zaoli Jiang 2 and Yung-Chi Cheng1
1Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
2PhytoCeutica, Inc. New Haven, Connecticut 06511, USA.
 
P-gp170 is a protein which causes multidrug resistance (MDR) phenotype in cancer and is also responsible for the poor oral uptake of certain compounds into circulation or brain through intestine or blood-brain barrier, respectively. The search for chemicals that inhibit P-gp170 is pursued by many laboratories around the world.
 

Chinese herbal medicine are taken orally and often formulated based on the principle of using one or more herbs to facilitate the action of other herbs. One of the underlying mechanisms by which this facilitation occurs, may be the inhibition of P-gp170 in the intestine by one herb thus enhancing the oral bioavailability of the compounds from other herbs.
 
To test this hypothesis, we selected one commonly used herb, Scutellaria baicalensis Georgi (Scute), to examine its impact on P-gp170 in KB/MDR, a P-gp170 overexpressing cell line. The accumulation of vinblastine in the KB/MDR cells was increased after treatment with Scute extract in a dose-dependent manner. One of the active compounds of the Scute is baicalein, it has a maximum inhibition level that is nearly same as verapamil. However, the 7-glucuronosyl form of baicalein, which is the most abundant compound in the Scute, did not show anti-MDR function.
 
Since herbals are generally taken orally, we treated the Scute and baicalein using a condition mimicking the physiological gastrointestinal environment (YCC treatment). Under this condition, baicalein no longer had the anti-MDR activity. In contrast, Scute under the same condition continued to exhibit the anti-MDR activity. Analysis of the samples indicates that the baicalein peak disappeared after YCC treatment while 70% of the peak of baicalein in the Scute extract remained after YCC treatment. This result suggests that baicalein in the herbal extract would be  more stable when passing through the stomach than pure baicalein compound. Sometimes chemicals in crude extracts are a better way for oral administration than in their pure form. To test whether Scute could increase the oral bioavailability of compounds which otherwise would be poorly absorbed because of the MDR pump, we used a Caco-2 cell transepithelial transport system which mimics the cellular layer of intestinal tract. Scute increased the amount of vinblastine passing through the Caco-2 monolayer in a dose-dependent manner.
 
In conclusion, Scute, but not its active compound, baicalein, may enhance the oral bioavailability of anticancer drugs or other chemicals which are substrates of MDR. Once baicalein from the Scute is in circulation, it may also overcome the MDR phenotype of cancer cells to chemotherapy and also enhance the uptake of drugs which are substrates of MDR through blood brain barrier. Since other herbs also have baicalein, these herbs should have the same potential as Scute to overcome MDR function.
 

National Meeting of the American Association of Cancer Research
Washington D.C, July 11-14, 2003.